Clinical Trial: A Safety Study of GSK3039294 in Healthy Volunteers and Patients With Systemic Amyloidosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Three-part Open-label, Non-randomised, Dose-escalation Study to Investigate the Safety and Tolerability of GSK3039294 Administered as a Single Dose to Healthy Volunteers, and as Repeat Dose to Healt

Brief Summary: GSK3039294 has been developed in order to offer an orally available alternative to parenteral CPHPC (GSK2315698 [metabolite of GSK3039294]) for plasma serum amyloid P component (SAP) depletion prior to use of anti SAP monoclonal antibody (mAb) in the treatment of systemic amyloidosis. This phase 1 study is intended to study safety, tolerability and pharmacokinetic (PK) profile of GSK3039294 in humans. This study consists of three parts. Part A will evaluate safety and tolerability of single doses of GSK3039294 in healthy subjects, Part B will evaluate safety and tolerability of repeat doses of GSK3039294 in healthy subjects, and Part C will evaluate safety and tolerability of repeat doses of GSK3039294 in subjects with systemic amyloidosis. Part A is a single dose, open label, dose escalation study. Two cohorts of subjects will be enrolled to provide data from 6 subjects per cohort and up to 4 different doses (2 dose levels per cohort) of GSK3039294 will be tested. For Cohorts 1 and 2, each subject may take part in two dosing periods. Part B is repeat dose, open label, dose escalation study. Sufficient number of subjects will be enrolled in Cohort 3a to ensure 6 completers (Cohort 3b will be conducted if required) and GSK3039294 will be administered repeatedly for a total of 21 days. Each subject will take part in a single study period. In Part C a single dose level of GSK3039294 will be tested for 21 days repeat dose, in 12 subjects with systemic amyloidosis. Each subject will take part in a single study period. The total duration for Part A is approximately 8 weeks, Part B is approximately 8-9 weeks, and Part C is approximately 13 weeks.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Part A: Number of subjects with any adverse events (AE) [ Time Frame: Approximately 5 weeks ]
    An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
  • Part A: Composite of hematology parameters as a measure of safety and tolerability [ Time Frame: Approximately 8 weeks ]
    The following hematology parameters will be measured: Platelet Count, red blood cell (RBC) Count, Hemoglobin, Hematocrit, Prothrombin Time, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cells (WBC) count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils
  • Part A: Composite of clinical chemistry parameters as a measure of safety and tolerability [ Time Frame: Approximately 8 weeks ]
    The following clinical chemistry parameters will be measured: blood urea nitrogen (BUN), Creatinine, Glucose, Phosphate, Potassium, Sodium, Calcium, Bicarbonate, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, Total and direct bilirubin, Total Protein, and Albumin
  • Part A: Composite of urinalysis parameters as a measure of safety and tolerability [ Time Frame: Approximately 8 weeks ]
    Specific gravity, power of hydrogen (pH), glucose, protein, blood and ketones measured by dipstick; and microscopic examination (if blood or protein in healthy subjects is abnormal)
  • Part A: Electrocardiogram (ECG) as a measure of s

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Part A: Maximum observed plasma concentration (Cmax) of GSK3039294 and GSK2315698 [ Time Frame: Pre-dose, and 0.25; 0.5; 0.75; 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 12; 16; 24 and 48 hrs post-dose during both periods ]
    • Part A: Area under the plasma concentration versus time curve (AUC) of GSK3039294 and GSK2315698 [ Time Frame: Pre-dose, and 0.25; 0.5; 0.75; 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 12; 16; 24 and 48 hrs post-dose during both periods ]
    • Part B: Cmax of GSK3039294 and GSK2315698 [ Time Frame: Day 1, 2-5, 8-11, 15-18, 21, and a single sample on 7-14 days post last dose ]
      Blood samples will be collected on Day 1: pre-dose, and 2 hour post-dose; Day 2 and 3: pre-dose; Day 4: pre-dose, and 0.5; 1; 2; 3; 4; 6 hours post-dose; Day 5: pre-dose, and 0.5; 1; 2; 3; 4; 6 hours post-dose; Day 8-11: pre-dose (before 1st dose of the day only); Day 15-18: pre-dose (before first dose of the day only); Day 21: pre-dose, and 0.5; 1; 2; 3; 4; 6; 8 and 12 hours post-dose (first dose of the day); and Follow-up (7 - 14 days post-dose): single sample
    • Part B: AUC of GSK3039294 and GSK2315698 [ Time Frame: Day 1, 2-5, 8-11, 15-18, 21, and a single sample on 7-14 days post last dose ]
      Blood samples will be collected on Day 1: pre-dose, and 2 hour post-dose; Day 2 and 3: pre-dose; Day 4: pre-dose, and 0.5; 1; 2; 3; 4; 6 hours post-dose; Day 5: pre-dose, and 0.5; 1; 2; 3; 4; 6 hours post-dose; Day 8-11: pre-dose (before 1st dose of the day only); Day 15-18: pre-dose (before first dose of the day only); Day 21: pre-dose, and 0.5; 1; 2; 3; 4; 6; 8 and 12 hours post-dose (first dose of the day); and Follow-up (7 - 14 days post-dose): single sample
    • Part B: Plasma SAP levels [ Time Frame: Day 1, 2-5, 8-11, 15-18, 21, and a single sample on 7-14 days post last dose ]
      Blood samples will be collected on Day 1: pre-dose, and 2 hour post-dose; Day 2 and 3: pre-dose; Day 4: pre-dose, and 0.5; 1; 2; 3; 4; 6 hours post-dose; Day 5: pre-dose, and 0.5; 1; 2; 3; 4; 6 hours post-dose; Day 8-11: pre-dose (before 1st dose of the day only); Day 15-18: pre-dose (before first dose of the day only); Day 21: pre-dose, and 0.5; 1; 2; 3; 4; 6; 8 and 12 hours post-dose (first dose of the day); and Follow-up (7 - 14 days post-dose): single sample
    • Part C: Cmax of GSK3039294 and GSK2315698 [ Time Frame: Day 1-21 and one sample/week on first 2 weeks post last dose ]
      Blood samples will be collected on Day 1: pre-dose, and 0.25; 0.5; 0.75; 1; 1.5; 2; 3; 4; 5; 6; 8; 10 and 12 hours post-dose; Day 2-7: pre-dose (before 1st dose of the day only); Day 8-20: pre-dose (before 1st dose of the day only) on days that a visit is planned; Day 21: pre-dose, and 0.5; 1; 2; 3; 4; 6; 8 and 12 hours post-dose (1st dose; note: 12 hour post dose sample to be taken before next dose administration); and during Follow-up: 1 sample/week (for first 2 weeks only).
    • Part C: AUC of GSK3039294 and GSK2315698 [ Time Frame: Day 1-21 and one sample/week on first 2 weeks post last dose ]
      Blood samples will be collected on Day 1: pre-dose, and 0.25; 0.5; 0.75; 1; 1.5; 2; 3; 4; 5; 6; 8; 10 and 12 hours post-dose; Day 2-7: pre-dose (before 1st dose of the day only); Day 8-20: pre-dose (before 1st dose of the day only) on days that a visit is planned; Day 21: pre-dose, and 0.5; 1; 2; 3; 4; 6; 8 and 12 hours post-dose (1st dose; note: 12 hour post dose sample to be taken before next dose administration); and during Follow-up: 1 sample/week (for first 2 weeks only).
    • Part C: Plasma SAP levels [ Time Frame: Day 1-21 and one sample/week on first 2 weeks post last dose ]
      Blood samples will be collected on Day 1: pre-dose, and 0.25; 0.5; 0.75; 1; 1.5; 2; 3; 4; 5; 6; 8; 10 and 12 hours post-dose; Day 2-7: pre-dose (before 1st dose of the day only); Day 8-20: pre-dose (before 1st dose of the day only) on days that a visit is planned; Day 21: pre-dose, and 0.5; 1; 2; 3; 4; 6; 8 and 12 hours post-dose (1st dose; note: 12 hour post dose sample to be taken before next dose administration); and during Follow-up: 1 sample/week (for first 2 weeks only).
    • Part C: Time to repletion of SAP [ Time Frame: Day 1-21 and one sample/week on first 2 weeks post last dose ]
      Blood samples will be collected on Day 1: pre-dose, and 0.25; 0.5; 0.75; 1; 1.5; 2; 3; 4; 5; 6; 8; 10 and 12 hours post-dose; Day 2-7: pre-dose (before 1st dose of the day only); Day 8-20: pre-dose (before 1st dose of the day only) on days that a visit is planned; Day 21: pre-dose, and 0.5; 1; 2; 3; 4; 6; 8 and 12 hours post-dose (1st dose; note: 12 hour post dose sample to be taken before next dose administration); and during Follow-up: 1 sample/week (for first 2 weeks only).


    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: November 9, 2015
    Date Started: May 12, 2016
    Date Completion: October 17, 2017
    Last Updated: May 18, 2017
    Last Verified: May 2017